This application, entitled Molecular Epidemiology and Viral Evolution in HIV-2 and HIV-1/HIV-2 Dually Infected Individuals in Senegal, for a K08 Mentored Clinical Scientist Development Award, will help enable Dr. Geoffrey S. Gottlieb, under the sponsorship of Dr. James I. Mullins and collaborators at the University of Washington School of Medicine and the University of Dakar, Senegal, to acquire the skills necessary to continue to pursue the immediate goals of this research plan as well as to continue his path toward an innovative and productive independent academic research career as a physician-scientist. A global understanding of the diversity and evolution of Human Immunodeficiency Viruses (HIVs) will be important to developing prophylactic vaccines and understanding the pathogenesis of AIDS. Although structurally and genetically similar, HIV-1 and HIV-2, behave quite differently, both at the level of the individual patient and as agents of the global epidemic. The reasons for this are not clear. Evidence suggests that patients dually infected with both HIV-1 and HIV-2 have greater control of their viral burden. Our longitudinally followed cohort of Senegalese individuals whom are infected with HIV-1, HIV-2 or both viruses provides a unique opportunity to study the molecular epidemiology and evolutionary dynamics of AIDS in West Africa and to correlate them with virologic, immune and clinical outcomes. This application will examine the following hypotheses: 1) If intra-patient, HIV-2 viral diversity and divergence will be attenuated compared to that seen in HIV-1 and if the rate of HIV evolution, as measured by viral divergence and diversity, will be slower in dually infected individuals. Whether emergence of CXCR4 HIV-1 variants will be delayed in dually infected individuals and whether these events correlate with immune status, viral load and clinical outcomes; 2) That cross-reactive immune responses and viral interference between HIV-1 and HIV-2 selects for infection with unique HIV-1 subtypes in dually infected individuals; and 3) If recombinant HIV-1/HIV-2 viruses can emerge in dually infected individuals and if they do, whether they alter the natural history of HIV infection in these people.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Investigator Award (CIA) (K08)
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Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
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Young, Janet M
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Whitham, Hilary K; Hawes, Stephen E; Chu, Haitao et al. (2017) A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa. Cancer Epidemiol Biomarkers Prev 26:886-894
Gottlieb, Geoffrey S; Eholie, Serge-Paul; Nkengasong, John N et al. (2008) A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa. AIDS 22:2069-72;discussion 2073-4
Herbeck, Joshua T; Gottlieb, Geoffrey S; Li, Xiuhong et al. (2008) Lack of evidence for changing virulence of HIV-1 in North America. PLoS One 3:e1525
Gottlieb, Geoffrey S; Nickle, David C; Jensen, Mark A et al. (2007) HIV type 1 superinfection with a dual-tropic virus and rapid progression to AIDS: a case report. Clin Infect Dis 45:501-9
Gottlieb, Geoffrey S; Nickle, David C; Jensen, Mark A et al. (2004) Dual HIV-1 infection associated with rapid disease progression. Lancet 363:619-22
Gottlieb, Geoffrey S; Sow, Papa Salif; Hawes, Stephen E et al. (2003) Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal, West Africa. AIDS Res Hum Retroviruses 19:575-84
Gottlieb, Geoffrey S; Sow, Papa Salif; Hawes, Stephen E et al. (2002) Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa. J Infect Dis 185:905-14